Effect of JTV-506, a Novel Vasodilator, on Experimental Angina Model in Rats

Hirata, Yukiya; Miyai, Hisato; Mabuchi, Yukiyo; Aisaka, Kazuo

doi:10.1097/00005344-199802000-00020

Cited by 11 publications

(6 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…15,16) As a result of the intravenous administration of lercanidipine, compared with nifedipine, benidipine and amlodipine in vasopressin-induced models, lercanidipine produced dose-dependent suppressive effects on the ST-depression, and its potency was higher than nifedipine and amlodipine. These effects occurred parallel to the suppressive effect on BPm, so it was suggested that these effects resulted from vasorelaxation on the basis of calcium channel antagonism.…”

Section: Discussionmentioning

confidence: 99%

Antianginal Effects of Lercanidipine on the Vasopressin or Methacholine Induced Anginal Model in Rats

Sasaki

Makino

Kase

et al. 2005

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

Angina pectoris is caused by an imbalance between the supply and demand for oxygen in the heart, and it is divided into Angina of Effort and Stable Angina depending on the cause of the anginal fit. The former is a situation of myocardial ischemia induced by a lack of oxygen, which is caused by an inability to increase blood flow due to coronary constriction. The latter is a situation of severe myocardial ischemia induced by coronary spasm or abnormal strain in periods of rest.1) Above all, in cases where anginal fit is frequent at daybreak or in the early morning, and a marked elevation of the ST segment from electrocardiography (ECG) is observed, it is called Variant Angina. ECG is used for an important diagnostic method for these diseases, because myocardial ischemia is closely reflected to changes on ECG such as elevation or depression in the ST segment.2) There are cases of these diseases where they occur alone or together; it cannot be classified simply, but regardless, a decrease in the oxygen demand and an increase in the myocardial blood flow are required in therapy.The clinical treatment of angina pectoris is mainly based on three groups of drugs, nitrates, b-adrenoceptor antagonists and calcium antagonists, which lead to the depression of oxygen consumption or the elevation of oxygen supply. The antianginal effect of calcium antagonists may be explained by their coronary dilatory effect (leading to the elevation of oxygen supply), cardio depressive effect (leading to the decrease of oxygen consumption) or the reduction of cardiac afterload according to antihypertensive effect.3,4) Based on their chemical structure, the compounds selective for slow calcium channels are divided to three subgroups; dihydropyridine (ex. nifedipine), benzothiazepine (ex. diltiazem) and phenylalkylamine (ex. verapamil). Recently, a second or third generation of dihydropyridine derivatives has been developed with the aim of providing greater vascular selectivity and a longer duration of action in order to allow a once-a-day dosage.A new 1,4-dihydropyridine derivative, lercanidipine (Fig. 1), synthesized at the Recordati Research Laboratory, is characterized by high vascular selectivity, 5) a slow-onset and a long duration of the antihypertensive effect.6,7) These characteristics may qualify lercanidipine as a useful drug for the treatment of essential hypertension and angina pectoris. Fifty eight nations have approved this drug for clinical use as an antihypertensive, and clinical trials have progressed in Japan. Clinical trials of the antianginal effect have also progressed in Europe, and previous data reveal the great potential of this drug for clinical use. 8) In this study, the possible target of the antianginal effect of lercanidipine was investigated using two models of angina pectoris with reference to nifedipine, benidipine and amlodipine. Nishitokyo, Tokyo 202-8585, Japan. Received November 25, 2004; accepted February 12, 2005 The antianginal effects of lercanidipine, a newly synthesized 1,4-dihydropyridine deriv...

show abstract

Section: Discussionmentioning

confidence: 99%

Antianginal Effects of Lercanidipine on the Vasopressin or Methacholine Induced Anginal Model in Rats

Sasaki

Makino

Kase

et al. 2005

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

show abstract

“…We have demonstrated that JTV-506 increases coronary blood flow with slight changes in blood pressure and heart rate when given intravenously and orally in conscious dogs [2]. JTV-506 also produces dose-dependent relaxation of large coronary arteries in vitro and in vivo [3] and shows an antianginal affect in experimental angina models in rats [4]. In the present study, we examined the myocardial and vascular effects of JTV-506 and compared them with those of antianginal drugs.…”

Section: Introductionmentioning

confidence: 93%

Cardiovascular Pharmacological Studies on JTV-506, a New Potassium Channel Opener

Hirata

Suzuki

Miyai

et al. 2011

Arzneimittelforschung

Self Cite

View full text Add to dashboard Cite

The effects of JTV-506 ((-)-(3S,4R)-2,2-bis(methoxymethyl)-4-[(1,6-dihydro-1-methyl-6-oxo-3- pyridazinyl)amino]-3-hydroxychroman-6-carbonitrile hemihydrate, CAS 170148-29-5), a novel coronary vasodilator, on hemodynamics, cardiac function and cardiac oxygen consumption were evaluated in anesthetized dogs. In anesthetized, open-chest dogs, JTV-506 (0.3-10 micrograms/kg i.v.) induced a marked increase in coronary blood flow in a dose dependent manner, while at these doses it had smaller effects on vertebral and mesenteric blood flow and almost no effect on renal blood flow. JTV-506 (1-10 micrograms/kg i.v.) showed a tendency to decrease oxygen consumption of the heart and elevate myocardial oxygen pressure without cardiac suppression. Effects of JTV-506 on hemodynamics and the respiratory system following i.v. administration (0.3-300 micrograms/kg) were investigated in spontaneously breathing anesthetized dogs. The effective dose to induce hemodynamic changes was more than 3 micrograms/kg. JTV-506 did not have a crucial influence on electrocardiogram. JTV-506 caused marked increase in coronary blood flow and myocardial oxygen pressure with slight change in blood pressure. It is concluded that JTV-506 is a potent vasodilator, with particularly pronounced effect on vasculature of the heart. These results suggest that JTV-506 may be useful in the treatment of angina pectoris.

show abstract

“…The antianginal eŠects of the drugs were assessed according to the method of Hirata et al 6) Rats were anesthetized with sodium pentobarbital (60 mg/ kg, i.p.). The standard limb lead II electrocardiogram (ECG) was recorded to measure S-wave depression.…”

Section: Ešects On Vasopressin-induced Angina Model In Ratsmentioning

confidence: 99%

“…4) AVP-induced angina is a useful model for evaluating the e‹cacy of compounds in vasospastic angina. [5][6][7][8] Karasawa et al 5) reported that benidipine has beneˆ-cial eŠects in various experimental angina models, including the AVP-induced angina model. We have demonstrated recently that the antianginal e‹cacy of benidipine 10 mg/kg was similar to that of diltiazem 1000 mg/kg in the AVP-induced angina rat model, indicating that benidipine exerts potent antivasospastic anginal eŠects.…”

Section: Introductionmentioning

confidence: 99%

Effects of Benidipine in a Rat Model of Experimental Angina

2006

View full text Add to dashboard Cite

To compare the antianginal eŠects of 1,4-dihydropyridine-type calcium-channel blockers, we evaluated the eŠects of benidipine, amlodipine, nifedipine, and efonidipine on vasopressin-induced myocardial ischemia in rats, an experimental model of angina. Intravenous administration of benidipine (3 mg/kg), amlodipine (1000 mg/kg), and nifedipine (100 mg/kg) suppressed the vasopressin-induced S-wave depression, an index of myocardial ischemia. Efonidipine (100 mg/kg, i.v.) tended to inhibit the S-wave depression. At the antianginal dose of each drug, amlodipine, nifedipine, and efonidipine decreased blood pressure signiˆcantly, whereas benidipine had little eŠect on blood pressure at a dose of 3 mg/kg. These results indicate that benidipine, unlike the other 1,4-dihydropyridine-type calcium-channel blockers examined in this study, inhibits vasopressin-induced coronary vasospasm with fewer undesirable eŠects such as hypotension in rats, suggesting that benidipine may be useful in the treatment of angina pectoris.

show abstract

Effect of JTV-506, a Novel Vasodilator, on Experimental Angina Model in Rats

Cited by 11 publications

References 14 publications

Antianginal Effects of Lercanidipine on the Vasopressin or Methacholine Induced Anginal Model in Rats

Antianginal Effects of Lercanidipine on the Vasopressin or Methacholine Induced Anginal Model in Rats

Cardiovascular Pharmacological Studies on JTV-506, a New Potassium Channel Opener

Effects of Benidipine in a Rat Model of Experimental Angina

Contact Info

Product

Resources

About